Dihydropyrazoles

There are four possible pyrazol-3-(Mie structures I-IV. The nomenclature most frequently used in the literature has been taken from Chemical Abstracts, wlwre for example, structure I is named 2,3-dihydropyrazol-3(lW)-(Mie and structure II is named 4,5-dihydropyrazol-5(l//)-one. Compounds I and II have also been named as pyrazolinones. Compounds with structure IV have been referred to as 2,3-diaza-2,4-cyclopentadienones. To avoid this needless confusion, the nomenclature used throughout this review is in accord with the recommendations set forth by lUPAC. 

Methyl-5-oxo-l-phenyl-4,5-dihydropyrazol-4-ylidene)-2,3-dihydro-l//-azepine (3), formed in 62% yield by the condensation of 2-amino- or 2-butoxy-37/-azepine with 3-methyl-l-phenylpyrazol-5(4//)-one, with Meerwein s reagent yields the tetrafluoroborate salt 4 which, on treatment with sodium dihydrogen phosphate, liberates the free base 5.64... 

An alternative strategy for generating 4,5-dihydropyrazoles is to perform 1,3-dipo-lar cydoaddition reactions of nitrile imines and alkenes. Langa and coworkers have... 

Pyrazole was hydrogenated over palladium on barium sulfate in acetic acid to 4,5-dihydropyrazole (A -pyrazoline), and 1-phenylpyrazole at 70-80° to 1-phenylpyrazolidine [478]. In benzopyrazole (indazole) and its homologs and derivatives the six-membered ring is hydrogenated preferentially to give... 

The belief that ring transformations of 1,2,4-oxadiazoles require an vinyl substituent in the 3-position had to be abandoned when it was found that compounds like (47) with saturated side chains undergo smooth ring transformation to 4,5-dihydropyrazoles (Scheme 16) <79JCR(S)64, 79JCR(M)801>. 

Fig. 4.13. illustrates how to apply carbon-13 NMR for analysis of tautomerism in heterocyclic chemistry 3-Methyl-5-oxo-l-phenyl-4,5-dihydropyrazole (the Knorr-pyrazolone ) is shown to exist as the CH tautomer B with a CH2 carbon at 43.1 ppm in chloroform solution (Fig. 4.13(a)), while the OH tautomer A predominates (90%) in hexadeuteriodimethyl sulfoxide (Fig. 4.13(b) [73 i]. 

Tables 15 and 16 give some available chemical shifts for azolines and azolidines, respectively. Unfortunately, data for many of the parent compounds are lacking, sometimes because the compounds themselves are unknown. The HNMR spectra of 128 4,5-dihydropyrazoles have been reported <1990JCM200>. Additive contributions of...

Dihydroimidazoles, -oxazoles, and -thiazoles 463, and their benzo derivatives 464, are all very easily aromatized (e.g., 464 465), and syntheses which might be expected to yield such dihydro compounds often afford the corresponding aromatic products. Among reagents which can be used for aromatization of 4,5-dihydropyrazoles are chloranil in... 

Dihydropyrazoles are converted into pyrazoles by oxidation with bromine or Pb(OAc)4 and they can also be dehydrogenated with sulfur. 3,5-Diphenylpyrazoline 469 on heating with platinum disproportionates to the pyrazole 470 and the pyrazolidine 471. 

Dihydropyrazoles have been used as models of intramolecular dyotropy. By combining primary deuterium kinetic isotope effects and X-ray crystallography, polycyclic systems, like 476, were shown to undergo a double proton transfer to produce 477. 

Dihydropyrazoles and -isoxazoles 502 (Z = NH, O) are cyclic hydrazones and oximes, respectively. 4,5-Dihy-dropyrazoles are quaternized at the 1-position (502 503). 2,3-Dihydro-l,3,4-oxadiazoles (e.g., 504) are very easily ring opened hydrolytically. 

Liu XJ, Cui P et al (2008) Synthesis, structure and antibacterial activity of novel l-(5-substituted-3-substituted-4, 5-dihydropyrazol-l-yl)ethanone oxime ester derivatives. Bioorg Med Chem 16 4075 82... 

The basicity of simple 4,5-dihydropyrazoles (A -pyrazolines) has been discussed on the basis of protonation at N-1 in the case of 1-unsubstituted, 1-methyl, and 1-phenyl derivatives <2000JP0372>. The pA values of 15 4,5-dihydropyrazoles substituted at N-1 by /i-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl groups were determined. After examining some linear free energy relationships, to discuss these values further, DFT calculations, including temperature effects, were carried out on the parent compounds (no C-substituents) for the 1-unsubstituted, 1-methyl, 1-phenyl, l-/)-nitrophenyl, and 1-(2,4,6-trinitrophenyl) series. These calculations predicted an inversion of N-1 and N-2 basicities between 1-phenyl- and l-(/>-nitrophenyl)-4,5-dihydropyrazoles. Since there were no experimental data for the protonation of 4,5-dihydropyrazoles in the gas phase, chemical ionization mass spectrometry was used to try to determine the structure of protonated 1-methyl- and l,3-dimethyl-5-phenyl-4,5-dihydropyrazoles. The substituent effects and protonation sites of 1-phenyl-3-methyl-5-A-benzylideneaminopyrazoles were studied by NMR and ab initio (6-31G ) MO calculations <1996J(P2)2383>. 

Microwave-assisted cyclocondensation of arylhydrazines 600 with alkyl dihalides or ditosylates 601 in aqueous media afforded 4,5-dihydropyrazoles 602 (Equation 123) <2005TL6011>. Reaction of phenylhydrazine 603 with 1,3-dibromo-2-propanol 604 under the same conditions afforded the 1-phenyl-l//-pyrazole 605 (Equation 124) <2006JOC135>. 

Dihydropyrazoles can be prepared under microwave irradiation conditions. /3-Alkyl chalcones 649 reacted with hydrazines under microwave conditions followed by addition of acid chlorides to yield 1-acyl-3,5-diaryl-5-alkyl-4,5-dihydropyrazoles 650 (Scheme 82) <2004TL1489>. l,3,5-Trisubstituted-2-pyrazolines 652 were obtained from chalcones 651 and phenylhydrazine on silica gel and with microwave irradiation (Equation 135) <2005JHC157>. 

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